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PubMed2004

Genotypic analysis of sequential genital herpes simplex virus type 1 (HSV-1) isolates of patients with recurrent HSV-1 associated genital herpes.

Clinical recurrences of Herpes simplex virus type 1 (HSV-1)-associated genital herpes are thought to be caused by reactivation of latent endogenous HSV-1. However, the possibility of reinfection with exogenous HSV-1 cannot be excluded. This study aimed to determine the incidence of genital HSV-1 superinfection in patients by investigating the genotype of sequential HSV-1 isolates obtained from the same anatomical site of patients with clinical recurrences of genital HSV-1 recurrent genital herpes. Sequential genital HSV-1 isolates were genotyped by PCR amplification of the hypervariable regions located within the HSV-1 genes US1 and US12. Whereas the sequential HSV-1 isolates in 11 of the 13 patients studied had the same genotypes, the sequential isolates of 2 patients showed a different genotype. The data suggest that HSV-1-induced recurrent genital herpes can be associated with genital reinfection with an exogenous HSV-1 strain.

Adult↗
PubMedDate not supplied

Prevalence of serum antibodies to herpes simplex virus types 1 and 2: application of an ELISA technique to 100 cases of anogenital herpes.

Sera of 100 patients affected by anogenital herpes were tested by an enzyme-linked immunosorbent assay (ELISA) technique using partially purified antigens obtained by extraction from the nuclei of infected Vero cells. Herpes simplex virus type 1 (HSV-1) was isolated from the anogenital lesions of 17 patients and herpes simplex virus type 2 (HSV-2) from 83 patients. The relative proportions of antibody of the IgG class to HSV-1 and HSV-2 were determined and their ratio (R) was calculated, except for 23 patients for whom the corrected optical density (COD) obtained for HSV-1 or HSV-2 antibody was less than the lower value limit of 0.025. A predominance of HSV-2 antibody (R less than 1) was found in 40 patients and was uniformly associated with isolation of HSV-2, whereas a predominance of HSV-1 antibody (R greater than 1) in 37 patients was found in the presence of infection with HSV-1 in 11 (30%) and with HSV-2 in 26 (70%) patients. This study also confirms the association of a higher frequency of recurrences with HSV-2: among the 55 patients with recurrent herpes, those from whom HSV-2 was isolated had a history of more recurrences than those infected with HSV-1 (P less than 0.05; Mann and Whitney's nonparametric test). No correlation between the number of recurrences and the level of HSV-2 antibody was found.

Antibodies, Viral↗
PubMed2004

Predictors of herpes simplex virus type 2 antibody positivity among persons with no history of genital herpes.

BACKGROUND: The demographic, historical, and behavioral factors that predict a positive herpes simplex virus type 2 (HSV-2) antibody test in persons without a history of genital herpes have not been well-defined. METHODS: Individuals (age 14-30 years) without a history of genital herpes completed a questionnaire and were offered free HSV-2 antibody testing. Factors from the questionnaire were correlated with the HSV-2 antibody result. RESULTS: Univariate analysis showed that female gender was significantly associated with positive test results. In gender-specific, multiple logistic regression models, a positive HSV-2 antibody test among men was associated with older age, non-white race, and a history of sexually transmitted disease (STD). Gender-specific symptom scores from the questionnaire were not predictive in either gender, but the gender-common symptom score was marginally predictive of a positive HSV-2 antibody test in women. Among women, older age, non-white race, and STD history predicted a positive test. CONCLUSIONS: Among young persons with no history of genital herpes who agreed to HSV-2 antibody testing, increasing age, non-white race, and a history of an STD were predictors of a positive test. A history of frequent pain, itching, burning, and rashes in the anogenital region was marginally associated with positive HSV-2 tests in women. These results might help guide selective use of HSV-2 antibody screening.

Adolescent↗
PubMed2007

Suppressive therapy with valacyclovir in early genital herpes: a pilot study of clinical efficacy and herpes-related quality of life.

BACKGROUND: Suppressive therapy has not been studied during the first year after acquisition of genital herpes, the time of maximum frequency of reactivation, potential for transmission, and impact on quality of life. OBJECTIVE: The objective of this study was to evaluate the effectiveness of suppressive therapy with valacyclovir initiated within 3 months of infection. STUDY DESIGN: The authors conducted a double-blind, randomized, controlled trial of 1.0 g valacyclovir daily versus placebo for 6 months in 119 patients. RESULTS: Herpes simplex virus (HSV) type 2 and HSV-1 were documented in 75 and 22 patients, respectively. In intention-to-treat analysis, annualized rates of symptomatic recurrences for valacyclovir and placebo, respectively, were 1.7 +/- 2.7 (mean +/- standard deviation) and 3.4 +/- 4.0 outbreaks per year (P = 0.012). Time to first recurrence was 80 +/- 47 days for valacyclovir and 54 +/- 49 days for placebo (P = 0.001). The differences in favor of valacyclovir were greatest in patients with confirmed HSV-2 infection. The Recurrent Genital Herpes Quality of Life score in HSV-2 infected patients rose 11.9 +/- 11.1 points for valacyclovir and 5.9 +/- 9.1 points for placebo (P = 0.040). CONCLUSIONS: Early suppressive therapy with valacyclovir reduces symptomatic recurrent outbreaks, especially in patients with HSV-2 infection. Valacyclovir therapy was associated with improved herpes-related quality of life.

Acyclovir↗
PubMed1992

Neonatal herpes simplex: Royal Women's Hospital 10-year experience with management guidelines for herpes in pregnancy.

In the 10-year period 1982-1991 inclusive, 6 cases of neonatal herpes simplex were diagnosed at the Royal Women's Hospital, Melbourne (1 disseminated, 1 pneumonitis, 4 cutaneous [1 with central nervous system involvement]), resulting in an incidence of 1 in 11,000 livebirths for this population. Three cases were due to HSV 1 and 3 to HSV 2. In no case did the mother have a recent or past history of overt genital herpes infection. Two cases were acquired in utero, an uncommonly recognized form of infection. A favourable long-term outcome occurred in 2 of 4 cases in which diagnosis was prompt and antiviral therapy was instituted rapidly. Routine antenatal screening in the last trimester of pregnant women with a history of genital herpes before pregnancy is not advised, because the results have been shown to be unreliable in predicting viral shedding and hence the infants' risk of exposure to virus at delivery. A protocol for management of herpes in pregnancy is included.

Acyclovir↗
PubMed1986

Activities of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine and its metabolites against herpes simplex virus types 1 and 2 in cell culture and in mice infected intracerebrally with herpes simplex virus type 2.

As measured by plaque and yield reduction assays, several metabolites of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) were highly active against herpes simplex virus types 1 and 2. These metabolites included the 2'-deoxy-2'-fluoroarabinosyl derivatives of 5-iodouracil (FIAU), cytosine (FAC), uracil (FAU), and thymine (FMAU). In mice inoculated intracerebrally with herpes simplex virus type 2, the relative order of potency of these compounds and licensed antiviral drugs was as follows: FMAU much greater than FIAC approximately equal to FIAU greater than acyclovir approximately equal to vidarabine much greater than FAC approximately equal to FAU. One of the main metabolites of FMAU, 2'-fluoro-5-hydroxymethyl-arabinosyluracil, was essentially inactive in vivo. FIAC-, FIAU-, FMAU-, FAC-, and FAU-resistant herpes simplex virus variants prepared in cell culture were found to be (i) devoid of viral thymidine kinase, (ii) cross-resistant to one another and resistant to drugs requiring viral thymidine kinase for activation, and (iii) sensitive to vidarabine or phosphonoformate. These results indicate that FIAC, FIAU, and FMAU require the virally encoded thymidine kinase for activation and suggest that the antiviral activity of FAU and FAC in cell cultures is also mediated by this enzyme. The interaction of the fluoroarabinosyl pyrimidine nucleosides with herpes simplex virus thymidine kinase in a cell-free system is also described.

Animals↗
PubMed1987

Enhanced method of herpes simplex virus culture confirmation using the virogen herpes slide test.

Of 100 herpes simplex virus specimens, 30% were detected by the Virogen Herpes Slide test at the initial observation of cytopathic effect (CPE) on MRC-5 cells. The remainder became positive after the CPE had progressed. Enhancement of the test procedure was accomplished by vortexing the infected cells to disrupt the monolayer, and the time to positivity became equivalent to the initial time of CPE. Compared with a fluorescent-antibody technique, the Virogen Herpes Slide test was 100% sensitive and specific when used for culture confirmation of herpes simplex virus.

Cytopathogenic Effect, Viral↗
PubMed1993

Value of serum anti-herpes simplex viral IgM antibody testing in empirical antiviral treatment of herpes simplex encephalitis.

Early antiviral treatment is important for herpes simplex encephalitis. A reliable test for supporting empirical therapy with antiviral agents is urgently needed. Sixty-six children with fever, focal seizures, and consciousness disturbance had their sera examined for anti-herpes simplex viral immunoglobulin M (IgM) antibody with enzyme-linked immunosorbent assay. The result was positive in all seven patients confirmed to have herpes simplex encephalitis. Only two of the other 59 patients were positive on this test. The average period for the development of serologic positivity was 7.3 days from the onset of neurologic symptoms. Although most sera were not tested in the early stage, all were collected on admission day. Our data suggest that before further evidence indicates another diagnosis, this simple, but specific IgM antibody test could be used as a guide for deciding to continue the antiviral treatment for serologically positive cases or to discontinue antiviral treatment for serologically negative ones. Yet, we would not suggest diagnosing herpes simplex encephalitis with this test alone.

Acyclovir↗
PubMed2006

Effect of valacyclovir on viral shedding in immunocompetent patients with recurrent herpes simplex virus 2 genital herpes: a US-based randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To determine the efficacy of daily suppressive therapy with a 1-g dose of valacyclovir in reducing total (clinical and subclinical) herpes simplex virus 2 (HSV-2) shedding compared with placebo in Immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes. PATIENTS AND METHODS: From June 18, 2004, to December 17, 2004, patients from 27 US sites with a history of 6 or more genital herpes recurrences per year were randomized in a 3:1 ratio to receive 1 g/d of valacyclovir or placebo. During the double-blind suppressive therapy, patients were provided with the study drug (500-mg valacyclovir caplets or matching placebo) and Instructed to take 2 caplets once daily without regard to meals for 60 days. Daily genital and anal or rectal swabs were self-collected during the 60-day study period for evaluation of HSV-2 viral shedding as determined by quantitative type-specific polymerase chain reaction assay. RESULTS: One hundred fifty-two patients were randomized into this study, 43 to placebo and 109 to 1 g/d of valacyclovir. A total of 134 completed the study (40 placebo [93%], 94 valacyclovir [86%]), and 18 prematurely withdrew (3 placebo [7%], 15 valacyclovir [14%]). Valacyclovir significantly reduced the percentage of days with total (clinical and subclinical) HSV-2 shedding throughout 60 days compared with placebo. In the intent-to-treat population, a 71% reduction in total shedding (P < .001), a 58% reduction in subclinical shedding (P < .001), and a 64% reduction in clinical shedding (P = .01) were observed. Valacyclovir was not associated with any significant toxic effects compared with placebo. CONCLUSION: This study demonstrated that 1 g/d of valacyclovir administered for 60 days was generally well tolerated and was an effective suppressive therapy that significantly reduced total (clinical and subclinical) HSV-2 shedding compared with placebo in immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes.

Acyclovir↗
PubMed1976

[Antibody titers--curse in patients with recurring Herpes simplex virus infections under vaccination with heat-inactivated Herpes viruses].

Follow-up studies of antibody-titres in patients suffering from recidivations of herpes labialis and progenitalis treated with herpes virus vaccine inactivated by heat. It was stated by several authors that patients suffering from recidivations of herpes labialis and progenitalis can be successfully treated with a herpes virus vaccine inactivated by heat (Lupidon G/H). Nothing is known, however, about the mechanisms diminishing recurrences. We have studied 11 patients and 3 control persons whether there were changes in specific antibody titres after repeated vaccinations. Skin reactions following intradermal injections were also tested. Serum samples studied over a period of 8 weeks until 9 months showed that the antibody titres found by complement-fixation and neutralization tests remained practically constant. Skin tests were always negative. Therefore it merits further study to find out the mode of action of this clinically successful treatment.

Antibodies, Viral↗
PubMed1990

Frequency of asymptomatic shedding of herpes simplex virus in women with genital herpes.

Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.

Adult↗
PubMedDate not supplied

[Indices of lymphocyte functional activity in patients with recurrent cutaneous-genital herpes during treatment with a herpes vaccine].

The functional activity of lymphocytes of patients with severe forms of recurrent cutaneous-genital herpes was studied in the course of treatment with inactivated polyvalent herpes vaccine on the basis of lymphocyte blast-transformation response to polyclonal mitogens and herpes simplex virus antigen. In the group of patients who showed a marked therapeutic effect as a result of the treatment the initially high values of the antigen-dependent lymphocyte blast-transformation test declined and became normal. Thus, in some cases the herpes vaccine exerts an immunomodulating effect normalizing the functions of different lymphocyte subpopulations.

Adult↗
PubMed1987

[Herpes simplex encephalitis with herpes simplex retinitis].

The association of herpes simplex encephalitis and herpes simplex retinitis is rare in adults. The case presented indicates that the manifestation of retinitis after herpes simplex encephalitis is infectious and not immunologic in origin. Retinal infection results either from neuron-to-neuron transmission of viruses along the optic nerve or from recurrent viral infection. Treatment with acyclovir improves the otherwise rather poor prognosis of combined herpes simplex encephalitis and retinitis. In this case a second course of systemic treatment with acyclovir was effective.

Adult↗
PubMed1987

Recurrent genital herpes on the buttocks: "herpes disciformis".

We report a clinical variety of recurrent genital herpes on the buttocks of seven women ranging in age from thirty-four to eighty-one years. The lesions had recurred for one to nine years and had produced a characteristic cicatricial rounded area within the S2 to S3 dermatomes on one buttock. Herpes disciformis is believed to be an anatomical variant of the common genital herpes infection. We have only noted it in middle-aged or older women with no history of genital herpes.

Adult↗
PubMed1978

[Herpes genitalis and herpes neonatorum (author's transl)].

This review discusses some basic virologic as well as epidemiologic aspects of herpes genitalis and herpes neonatorum. The clinical picture of herpes neonatorum is presented. At the moment, from the point of view of survival and of psycho-motoric development, the prognosis of this neonatal infection is poor. This fact, as well as the inability of therapeutic trials to modify the prognostic outlook, derive from the hitherto published experiences. Up to this time, the literature also fails to prove the validity of prophylactic cesarean section in preventing neonatal herpes simplex infection. Based on theoretical grounds, however, this prophylactic intervention seems still to be justified under specific circumstances. Repeated cervical smears toward the end of pregnancy are recommended: virologic cultures, whose results can often be communicated after 24 hours, are helpful in deciding if cesarean section is to be performed.

Cesarean Section↗
PubMed1983

Increase in laboratory-confirmed cases of herpes genitalis and neonatal herpes infections in Israel.

Jewish women have been considered to be at low risk for genital herpes simplex virus Type 2 (HSV-2) infections. During the period 1973 to 1981, genital herpes simplex infections were laboratory confirmed in 129 cases (81 women and 48 men). Until 1976, only sporadic cases were reported to our laboratory. Since then, the number of cases has gradually increased, reaching 31 new reported cases in 1981. The age distribution was typical for a sexually transmitted disease, with the peak of infection at childbearing age (20 to 39 years). As a result, rising morbidity of neonates--due to active genital herpes virus infection in the mother during delivery--could be expected, and monitoring of high-risk pregnancies for prevention of perinatal infections was introduced. Of 14 pregnant women monitored, herpesvirus was isolated in 4 in the last week before delivery, and cesarean section was advised. In addition, during the last 3 years, neonatal herpes was confirmed in six, and suspected in three neonates whose mothers were not monitored for genital herpesvirus infection during pregnancy.

Adult↗
PubMed1997

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

2-Aminopurine↗
PubMed2006

Herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive!

Infections of the skin by herpesviruses do not always present themselves in typical fashion. Conventional microscopy is used routinely to confirm infection by herpesviruses, but sometimes typical signs such as multinucleated epithelial cells or "ghosts" of them are not encountered in a specimen (so-called herpes incognito). We studied 35 patients in whom infection with herpesviruses was differentially diagnosed clinically but in whom a biopsy specimen had been taken for confirmation. Only those patients in whom histopathologic findings had been interpreted as being "not diagnostic" of herpesvirus infection by 2 independent dermatopathologists were included. Clinical and histopathologic findings were correlated with results from polymerase chain reaction studies on formalin-fixed paraffin-embedded tissue. Polymerase chain reaction revealed herpesvirus-specific DNA in 12 of 35 specimens, 10 being varicella zoster virus (VZV) positive, 1 herpes simplex virus (HSV)-2 positive, and 1 HSV-1 positive. Ten of these 12 cases presented themselves in very similar fashion (8 VZV, 1 HSV-1, 1 HSV-2). All lesions were macular or papular and typified mostly by dense perivascular and sparse interstitial superficial and deep infiltrates of lymphocytes, sometimes assuming a patchy lichenoid pattern. Infiltrates were prominent in and around adnexal structures, often peppering follicles, sebaceous glands, and eccrine glands. Lymphocytes were also found in the lower part of the epidermis accompanied by a combination of spongiosis and vacuolar alteration. The papillary dermis was often edematous; extravasated erythrocytes in variable numbers were a common finding. Lymphocytes sometimes had large and polygonal nuclei. Neutrophils and nuclear dust were present occasionally; eosinophils were rare. We conclude that herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive.

Journal Article↗